C-H Functionalization: The Hatakeyama Synthesis of (-)-Kaitocephalin

John F. Hartwig of the University of California, Berkeley showed
(Nature2012, 483, 70.
)
that intramolecular C-H silylation of 1
selectively gave, after oxidation and acetylation, the bis acetate 2.
Gong Chen of Pennsylvania State University coupled
(J. Am. Chem. Soc.2012, 134, 7313.
)
3 with 4 to give the ether 5.
M. Christina White of the University of Illinois effected
(J. Am. Chem. Soc.2012, 134, 9721.
)
selective oxidation of the taxane derivative 6
to the lactone 7.

Most of the work on C-H functionalization has focused on the formation of
C-C, C-O and C-N bonds. Donald A. Watson of the University of Delaware developed
(Angew. Chem. Int. Ed.2012, 51, 3663.
)
conditions for the complementary conversion of an alkene 8 to
the allyl silane 9, a powerful and versatile nucleophile.

As illustrated by the conversion of 18 to 20 devised
(Adv. Synth. Catal.2012, 354, 701.
)
by Martin Klussmann of the Max-Planck-Institut,
Mülheim, C-H functionalization can be accomplished by hydride abstraction
followed by coupling of the resulting carbocation with a nucleophile. Olafs
Daugulis of the University of Houston used
(Angew. Chem. Int. Ed.2012, 51, 5188.
)
a Pd catalyst to couple 21 with 22 to give 23
with high diastereocontrol. Yoshiji Takemoto of Kyoto University cyclized
(Angew. Chem. Int. Ed.2012, 51, 2763.
)
the chloroformate 24 directly to the oxindole 25.
Carlos Saá of the Universidad de Santiago de Compostela used
(Angew. Chem. Int. Ed.2012, 51, 723.
)
a Ru catalyst to add 27 to the alkyne 26, generating a metallocarbene
that cyclized to the cyclopentane 28.

To be used early in a multi-step preparation, a synthesis protocol must be
robust and easily scalable. It is a tribute to the power of the C-H amination
method developed by Justin Du Bois, exemplified by the cyclization of 29
to 30, that Susumi Hatakeyama of Nagasaki University was able to use it
(Org. Lett.2012, 14, 1644.
)
as a key step in a synthesis of (-)-Kaitocephalin
(31). This same C-H amination protocol was used again a little later in
that synthesis.